Drugs created for a specific condition—say, diabetes or psoriasis—one day may be able to help some lung cancer patients. Discovering a new use for old or existing drugs is the aim of current research looking to overcome drug resistance in lung cancer.
Most of the 225,000 people diagnosed with lung cancer in 2014 will have a type called non-small cell lung cancer. For about 10% of them, the tumors will be driven by a mutation in a gene called EGFR. Patients with EGFR-mutant lung cancer are often treated with Tarceva (erlotinib), a drug that inhibits the aberrant gene’s cancer-stimulating activities.
But nearly every tumor eventually develops resistance to Tarceva, says Curtis Chong, M.D., Ph.D., a medical oncology fellow at Dana-Farber Cancer Institute in Boston. Funded by a three-year, $163,500 grant from the American Cancer Society, Chong is now amassing a library of every targeted drug known to medicine. He’s testing each in combination with Tarceva to see if any can help the EGFR inhibitor resume its job of killing cancer cells.
“On average it takes up to 15 years and costs up to a billion dollars to make one new drug from scratch,” says Chong. “By screening drugs that are FDA-approved or have already been tested in clinical trials, this shortcut will allow us to decrease the time and expense of new drug discovery.”
He’s already acquired and catalogued 1,500 targeted drugs. By the time his collection is complete, Chong hopes to have at least 5,000. “My goal is to relentlessly track down every drug in the world and see if we can put it into our collection and test it,” he says.
Finding the Right Match
When a lung cancer patient at Dana-Farber stops responding to Tarceva, a small piece of tumor tissue is removed with a biopsy. In the lab, Chong uses the tumor sample to create a cell line—a colony of genetically identical cells—for drug testing.
He has found several effective pairings with Tarceva in the lab for two out of 20 Tarceva-resistant patients screened so far. The next step, he says, is to find the culprit gene that is driving tumor resistance in each patient. “We may then be able to develop a simple DNA test to identify patients with that specific mechanism of resistance,” says Chong.
Chong expects to have a genetic test and drug combination ready to test in clinical trials within several years.
Although the goal of his current research is to restore a tumor’s sensitivity to Tarceva, Chong anticipates patients with EGFR-mutant lung cancer could one day have their tumors tested for a particular predictor of Tarceva resistance. If they test positive for the specific mutation, a drug could be given along with Tarceva to prevent resistance from ever happening.
Repurposing drugs is not new. It’s the reason the acne drug retinoic acid is now a treatment for an acute form of leukemia. It’s why ketoconazole for fungal infections is also used in prostate cancer treatment. But what makes Chong’s research particularly significant is that he hopes to prolong Tarceva’s attack on lung cancer, which kills more Americans than any other cancer.
“We want to offer patients the largest panel of existing drugs that target almost every pathway that we can chemically inhibit,” he says. “Once we’re able to offer that, we can go after new ways to overcome drug resistance in lung cancer.”